LTD4 and bradykinin evoke endothelium-dependent relaxation of the renal vein: dissimilar mechanisms.

This study's goals were to define the vasomotor effects of the peptide leukotriene (LT)D4 on norepinephrine (NE)-contracted isolated rings of canine renal vein (RV) and to compare these influences with those of bradykinin (BK). Canine RV rings were connected to isometric force transducers and bathed in Krebs-Ringer bicarbonate buffer containing indomethacin (10-5M). LTD4 and BK evoked dose-dependent decreases in tone of NE-contracted RV rings that were abolished by physical removal of the endothelium. Relaxation of the RV ring produced by glyceryl trinitrate (GTN) was slightly enhanced or unaltered after endothelium denudation. Reduced human hemoglobin (Hb, 10(-6) M), NG-monomethyl-L-arginine (L-NMMA, 300 microM) and methylene blue (MB, 10(-6) M) had no effect on LTD4-induced venomotor relaxation, whereas they significantly decreased the vasorelaxant effect of BK. In contrast, endothelium-dependent relaxation of renal arterial rings produced in response to both LTD4 and BK was markedly attenuated in the presence of either reduced Hb (10(-6)M) or MB (10(-6) M). MB significantly attenuated venorelaxant responses to GTN (10(-8) to 10(-6) M). The ATP-sensitive K(+)-channel blocker glybenclamide (10(-6)M) inhibited relaxation of the RV induced by cromakalim (5 x 10(-8)M) but had no effect on LTD4-evoked relaxation. These data indicate that endothelium-dependent relaxation of the RV elicited by BK is dependent on "classic" endothelium-derived relaxing factor (EDRF) considered to be nitric oxide (NO) or an unstable nitroso compound that ultimately liberates the NO radical.(ABSTRACT TRUNCATED AT 250 WORDS)